/ Abstract This project - 'Performance Indices of Social Disability in Toddlers with Autism'- addresses Challenge Area '(04) Clinical Research'and Specific Challenge Topic 'Autism: Addressing the Challenge (04-MH-101*)';and Challenge Area '(01) Behavior, Behavioral Change, and Prevention'and Specific Challenge Topic 'Individual- Based Model of Social Behavior (01-GM-101*)'. The overarching goal of this project is to develop performance indices of social engagement which can be used at the earliest point of diagnosis to parse out heterogeneity of syndrome expression and identify predictors of outcome. We will collect eye-tracking data to quantify visual fixation and scanning during viewing of naturalistic social situations in N=80 12- to 24-month-old infants with autism spectrum disorders (ASD), non-autistic developmental delays, and typical development. The children's extensive clinical characterization at the time of the experiments will be supported by the Yale ACE, which will also support diagnostic confirmation and developmental assessment procedures to be obtained at ages 36 to 48 months, which is beyond the scope of this RC1. Based on a single, 5-minute behavioral assay, we will derive measures of (1) eye-blink inhibition as an index of stimulus salience;(2) attention shifting as an index of adaptive, social visual pursuit;and (3) social visual monitoring as an index of active pursuit of communicative intentions. Work supporting the utility of these three methods has involved 2- to 3-year-olds, school-age children, and adolescents with ASD. In this application, we extend our methods to the study of social engagement in the second year of life. This application builds on 7 years of pioneering work capitalizing on eye-tracking technology to measure spontaneous visual fixations and visual scanning during viewing of naturalistic social situations in over 420 individuals with ASD, from infancy through adolescence (U54- MH66494, P50 MH081756, and R01 MH083727, PI A Klin). Our specific aims address directly three major themes in the National Institutes of Health Interagency Autism Coordinating Committee: 'Heterogeneity of Autism Spectrum Disorders', 'Predictors of Outcome'and 'Biomarkers'. The vast variability of abilities and symptoms displayed by individuals with autism is one of the greatest challenges for research on its causes and treatment. Using eye-tracking technology, this project employs three novel and converging performance measures of social engagement to quantify social disability in a group of 12- to 24-month old infants with autism spectrum disorders and to assess their clinical utility. These measures are derived from one brief, 5-minute viewing of a commercial video portraying toddlers at play. The goal of this work is to quantify a core and defining symptom of autism during the period of earliest detection.